• 文章类型: Journal Article
    银屑病是一种常见的炎症性皮肤病,严重影响患者的生活质量。银屑病的诊断主要依据临床和病理特征,评估取决于银屑病面积和严重程度指数(PASI)。然而,很少有可靠和准确的评估方法来评估病变的严重程度和治疗效果。这项工作从GEO数据集中鉴定了17个模型基因,并通过LASSO回归建立了6个银屑病评估模型,线性回归,和随机森林分开。在不同的GEO数据集中对模型进行了训练和评估。所有6个模型在训练和测试数据中准确地分类了银屑病皮损和非皮损,并显示良好的AUC。在生物制品处理的样品中,模型评分与病变严重程度呈正相关,与治疗时间呈负相关。因此,模型具有评估治疗效果的潜力。此外,在角质形成细胞中检测模型基因的表达,IMQ诱导的银屑病小鼠的皮肤,和牛皮癣患者的病变。在细胞因子刺激的角质形成细胞和银屑病病变中,模型基因的RNA和蛋白质水平如预期的那样增加。这项工作提供了评估银屑病皮损严重程度和生物制剂治疗效果的新方法。
    Psoriasis is a common inflammatory skin disease that seriously affects the patient\'s quality of life. The diagnosis of psoriasis is mainly based on clinical and pathological features, and the assessment depends on the psoriasis area and severity index (PASI). However, there are few reliable and accurate evaluation methods to assess lesion severity and therapeutic effects. This work identified 17 model genes from GEO datasets and established 6 psoriasis evaluation models by LASSO regression, linear regression, and random forest separately. Models were trained and evaluated in different GEO datasets. All 6 models accurately classified psoriatic lesions and non-lesional skin in training and testing data, and showed good AUC. In biologics-treated samples, the model scores were positively correlated with the severity of lesions and negatively correlated with treatment length. Thus, models have the potential to assess the therapeutic effects. In addition, the expression of model genes was examined in keratinocytes, skin of IMQ-induced psoriatic mice, and lesions of psoriasis patients. The RNA and protein levels of model genes increased in cytokine-stimulated keratinocytes and psoriatic lesions as expected. This work provides new methods to assess the lesion severity and therapeutic effects of biologics in psoriasis.
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  • 文章类型: Case Reports
    Takayasu动脉炎(TA)是一种病因不明的自身免疫实体,可引起大中型动脉肉芽肿性增厚。常见症状包括跛行,头痛,头晕,晕厥,视觉变化,还有心悸.不同的心脏表现,比如缺血性心脏病,显著的主动脉瓣反流,肺动脉高压,与TA相关联,尽管它们很少表现为充血性心力衰竭。无线电成像,包括CT血管造影和MR血管造影,随着更具侵入性的程序,如传统的血管造影,通常用于诊断。用皮质类固醇治疗,类固醇保护剂,生物制剂,和血运重建程序。这里,有一例17岁的印度女性主诉腹痛.几年前她被诊断出患有桥本甲状腺炎,还有充血性心力衰竭的病史.在一般检查中,由于双侧颈动脉杂音的存在,上肢的血压不对称。所有四肢的伸肌表面也存在广泛的鳞片状病变,提示牛皮癣。放射成像证实了TA的诊断。CT血管造影还显示腹腔干和胃左动脉近端完全闭塞,这可能是她症状的原因.患者接受皮质类固醇联合甲氨蝶呤治疗,以及其他支持性药物。TA伴充血性心力衰竭在文献中偶尔有描述,而TA与牛皮癣的关联更为罕见。各种自身免疫性疾病的同时发生是常见的,但是桥本甲状腺炎的三合会,牛皮癣,与心脏衰竭的初始表现是独特的。由于自身免疫性疾病的共同发生,为了获得最佳的健康结果,必须进行早期和全面的患者评估和全面的研究。
    Takayasu arteritis (TA) is an autoimmune entity of unknown aetiology causing granulomatous thickening of large and medium-sized arteries. Common symptoms include claudication, headaches, dizziness, syncope, visual changes, and palpitations. Diverse cardiac manifestations, such as ischemic heart disease, significant aortic regurgitation, and pulmonary hypertension, are associated with TA, although they rarely manifest as congestive heart failure. Radio-imaging, including CT angiography and MR angiography, along with more invasive procedures such as conventional angiography, are often used for diagnosis. Treatment is done with corticosteroids, steroid-sparing agents, biologics, and revascularization procedures. Here, we have a case of a 17-year-old Indian female who presented to us with a complaint of abdominal pain. She was diagnosed with Hashimoto\'s thyroiditis a few years ago, along with a history of congestive heart failure. On general examination, blood pressure was asymmetrical in the upper limbs with the presence of bilateral carotid bruit. There was also the presence of extensive scaly lesions on the extensor surface of all four limbs, suggestive of psoriasis. Radio-imaging confirmed the diagnosis of TA. CT angiography also showed total occlusion of the celiac trunk and proximal left gastric artery, which was likely the cause of her symptoms. The patient received treatment with corticosteroids in conjunction with methotrexate, along with other supportive drugs. TA with congestive heart failure has been occasionally described in the literature, while the association of TA with psoriasis is much rarer. The simultaneous occurrence of various autoimmune diseases is common, but the triad of Hashimoto thyroiditis, psoriasis, and TA with an initial presentation of heart failure is unique. Due to the common co-occurrence of autoimmune conditions, early and thorough patient evaluation with comprehensive studies is imperative for optimal health outcomes.
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  • 文章类型: Journal Article
    皮肤是身体的重要屏障组织。必须精确控制皮肤中的免疫反应,否则会导致严重的疾病,如牛皮癣,特应性皮炎,或致病性感染。研究证据越来越多地证明了神经支配的重要作用,即,感觉和交感信号,调节皮肤免疫力。值得注意的是,在皮肤病中已经观察到这种神经结构的神经病变,暗示他们直接参与各种病理过程。深入了解皮肤神经病及其免疫调节作用的机制可能有助于揭示治疗干预的新切入点。这里,我们总结了神经性事件和皮肤免疫之间的神经免疫相互作用,强调这一新兴研究前沿的当前知识和未来观点。
    Skin is a vital barrier tissue of the body. Immune responses in the skin must be precisely controlled, which would otherwise cause severe disease conditions such as psoriasis, atopic dermatitis, or pathogenic infection. Research evidence has increasingly demonstrated the essential roles of neural innervations, i.e., sensory and sympathetic signals, in modulating skin immunity. Notably, neuropathic changes of such neural structures have been observed in skin disease conditions, implicating their direct involvement in various pathological processes. An in-depth understanding of the mechanism underlying skin neuropathy and its immunomodulatory effects could help reveal novel entry points for therapeutic interventions. Here, we summarize the neuroimmune interactions between neuropathic events and skin immunity, highlighting the current knowledge and future perspectives of this emerging research frontier.
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  • 文章类型: Congress
    暂无摘要。
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  • 文章类型: Journal Article
    牛皮癣,一种慢性免疫介导的皮肤病,影响全球超过1.25亿人,以异常的角质形成细胞增殖和免疫细胞浸润为特征。尽管光动力疗法(PDT)作为一种有希望和有效的治疗方法,但在牛皮癣的治疗中仍未得到充分利用。本研究旨在探讨酞菁锌(ZnPc)及其糖缀合物作为潜在抗银屑病药物的功效。我们成功合成了受保护和未受保护的糖共轭锌酞菁,并评估了它们对细胞因子刺激的HaCaT角质形成细胞的潜力。以及已建立的IMQ类银屑病体内模型。四取代的受保护的葡萄糖-ZnPc(Glu-4-ZnPc-P)与未受保护的葡萄糖缀合物(IC50=22.7µM)相比表现出优异的光毒性(IC50=2.55µM),受保护的半乳糖-ZnPc(IC50=7.13µM),和细胞因子刺激的HaCaT细胞中的游离ZnPc(IC50=5.84µM)。细胞摄取分析显示,IL-17A,一种在银屑病发病机制中起核心作用的细胞因子,未保护的Glu-4-ZnPc吸收增加56.3%,而GLUT1抑制剂BAY-876使其积累减少了23.8%。用IL-17A刺激后Glu-4-ZnPc-P-PDT后细胞内ROS的产生显着增加,与体外光细胞毒性相关。使用Glu-4-ZnPc-P的体内PDT显示银屑病面积和严重程度指数(PASI)的显着改善,抑制脾肿大,恢复正常皮肤形态。这项研究强调了糖共轭锌酞菁作为银屑病靶向性PDT的潜在候选者,为进一步的临床研究提供依据。
    Psoriasis, a chronic immune-mediated skin disorder affecting over 125 million people globally, is characterized by abnormal keratinocyte proliferation and immune cell infiltration. Photodynamic therapy (PDT) remains underutilized in the treatment of psoriasis despite its potential as a promising and effective therapeutic approach. This study aimed to explore the efficacy of zinc phthalocyanine (ZnPc) and its sugar conjugates as potential antipsoriatic agents. We successfully synthesized protected and unprotected sugar-conjugated zinc phthalocyanines and evaluated their potential against cytokine-stimulated HaCaT keratinocytes, as well as an established IMQ psoriasis-like in vivo model. Tetrasubstituted protected glucose-ZnPc (Glu-4-ZnPc-P) demonstrated superior phototoxicity (IC50 = 2.55 µM) compared to unprotected glucose conjugate (IC50 = 22.7 µM), protected galactose-ZnPc (IC50 = 7.13 µM), and free ZnPc in cytokine-stimulated HaCaT cells (IC50 = 5.84 µM). Cellular uptake analysis revealed that IL-17A, a cytokine that plays a central role in the pathogenesis of psoriasis, enhanced unprotected Glu-4-ZnPc uptake by 56.3%, while GLUT1 inhibitor BAY-876 reduced its accumulation by 23.8%. Intracellular ROS generation following Glu-4-ZnPc-P-PDT was significantly increased after stimulation with IL-17A, correlating with in vitro photocytotoxicity. In vivo PDT using Glu-4-ZnPc-P exhibited significant improvement in Psoriasis Area and Severity Index (PASI), inhibiting splenomegaly and restoring normal skin morphology. This study highlights sugar-conjugated zinc phthalocyanines as potential candidates for targeted PDT in psoriasis, providing a basis for further clinical investigations.
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  • 文章类型: Journal Article
    本研究探索开发和优化负载双嘧达莫和罗氟司特的纳米乳液(NE)系统,旨在改善皮肤渗透和保留。将NE制剂进一步转化为纳米乳液凝胶以增强其作为牛皮癣的局部治疗的应用。进行溶解度研究以选择油,表面活性剂,和助表面活性剂。使用水相滴定法构建相图。所有的配方都是纳米级的,和式(F2)(包含油酸油作为油相,除了以1:5:4的比例作为水相的蒸馏水之外,表面活性剂吐温80和助表面活性剂(乙醇)的比例为1:2的混合物)是根据粒度选择的配方,PDI,和zeta电位。配方(F2)具有最佳的比例,因为它给出了最小的纳米乳液球尺寸(平均粒径为167.1nm),最佳均匀性(最低PDI为0.195),和最高的稳定性(较高的zeta电位-32.22)。通过添加0.5%(w/w)黄原胶(平均粒度为172.7nm)和最佳均一性(0.121%的最低PDI)和最高稳定性(-28.31的较高ζ电位),将所选配方转化成纳米乳液凝胶。总之,选定的配方具有公认的物理和化学性质,增强皮肤渗透。
    This study explores developing and optimizing a nanoemulsion (NE) system loaded with dipyridamole and roflumilast, aiming to improve skin penetration and retention. The NE formulation was further transformed into a nanoemulgel to enhance its application as a topical treatment for psoriasis. Solubility studies were conducted to select the oil, surfactant, and co-surfactant. Phase diagrams were constructed using the aqueous phase titration method. All the formulations were in nanoscale, and Formula (F2) (which contains oleic acid oil as the oil phase, a mixture of Surfactant Tween 80 and co-surfactant (ethanol) at a ratio of 1:2 in addition to distilled water as an aqueous phase in a ratio of 1:5:4, respectively) was the selected formula depending on the particle size, PDI, and zeta potential. Formula (F2) has the best ratio because it gives the smallest nanoemulsion globule size (particle size average of 167.1 nm), the best homogenicity (lowest PDI of 0.195), and the highest stability (higher zeta potential of -32.22). The selected formula was converted into a nanoemulgel by the addition of 0.5% (w/w) xanthan gum (average particle size of 172.7 nm) and the best homogenicity (lowest PDI of 0.121%) and highest stability (higher zeta potential of -28.31). In conclusion, the selected formula has accepted physical and chemical properties, which enhanced skin penetration.
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  • 文章类型: Journal Article
    银屑病是一种慢性全身性疾病,具有多方面的病理机制和免疫学基础,皮肤炎症性病变和关节疾病的存在。伴随牛皮癣的疾病包括代谢和心血管疾病。已经提出炎症参与这些病症中的每一种的发展。这项研究的主要目的是分析脂肪酸谱,包括多不饱和脂肪酸,在牛皮癣患者的红细胞膜上。Szczecin的Pomeranian医科大学皮肤和性病系的58名成人患者,患有牛皮癣,有资格参加这项研究。患者接受了访谈和体检,在此期间评估银屑病的严重程度。测量所有患者的体重和身高以评估其体重指数(BMI)。治疗3个月后,生化参数(ALT,AST,评估血液中的总胆固醇)和炎症标志物(CRP)。此外,脂肪酸的分离(PUFA,SFA,来自红细胞膜的MUFA),并使用气相色谱仪对其进行了定性和定量分析。在需要全身治疗的严重银屑病患者中,发现红细胞膜中脂肪酸的变化,包括显著较低浓度的多不饱和脂肪酸(omega-3),具有抗炎作用;饱和脂肪酸的浓度显着升高;油酸(omega-9)的浓度降低,与接受局部治疗的较不严重的银屑病患者的结果相比。在银屑病和BMI≥25的患者中,血液中AST和ALT的浓度显着升高,红细胞膜中促炎花生四烯酸的浓度显着升高。饱和脂肪酸(R=0.31)和单不饱和脂肪酸(R=0.29)的浓度升高可能与牛皮癣的严重程度有关。
    Psoriasis is a chronic systemic disease with a multifaceted pathomechanism and immunological basis, with the presence of inflammatory skin lesions and joint ailments. Diseases accompanying psoriasis include metabolic and cardiovascular disorders. It has been suggested that inflammation is involved in the development of each of these conditions. The main objective of this study was to analyse the fatty acid profile, including polyunsaturated fatty acids, in the erythrocyte membranes of patients suffering from psoriasis. A total of 58 adult patients of the Department of Skin and Venereal Diseases of the Pomeranian Medical University in Szczecin, suffering from psoriasis, were qualified for this study. The patients had undergone an interview and physical examination, during which the severity of psoriasis was assessed. All patients had their weight and height measured to assess their body mass index (BMI). After 3 months of treatment, biochemical parameters (ALT, AST, total cholesterol) and inflammatory markers (CRP) in the blood were assessed. In addition, the isolation of fatty acids (PUFAs, SFAs, MUFAs) from erythrocyte membranes and the qualitative and quantitative analysis of their profile using a gas chromatograph were carried out. In patients with severe psoriasis requiring systemic treatment, an altered profile of fatty acids in erythrocyte membranes was found, including a significantly lower concentration of polyunsaturated fatty acids (omega-3), which have an anti-inflammatory effect; a significantly higher concentration of saturated fatty acids; and a decreased concentration of oleic acid (omega-9), compared to the results obtained in patients with less severe psoriasis receiving topical treatment. In patients with psoriasis and BMI ≥ 25, significantly higher concentrations of AST and ALT in the blood and significantly higher concentrations of pro-inflammatory arachidonic acid in erythrocyte membranes were found. Elevated concentrations of saturated (R = 0.31) and monounsaturated fatty acids (R = 0.29) may correlate with a greater severity of psoriasis.
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  • 文章类型: Journal Article
    背景:银屑病是一种常见的炎症性疾病,常伴有瘙痒和疼痛。本研究旨在评估银屑病患者皮肤疼痛的临床特点。材料:总共106名被诊断为牛皮癣的患者被纳入研究(34%为女性;平均年龄42.1±13.0岁)。使用牛皮癣面积和严重程度指数(PASI)评估疾病严重程度。使用数字评定量表(NRS)和4项瘙痒评分(4IIS)评估瘙痒严重程度。通过NRS测量皮肤疼痛的强度,简式麦吉尔疼痛问卷(SF-MPQ),视觉模拟量表(VAS),和DouleurNeuropathique-4问卷(DN4)。结果:在过去的一周中,84.9%的银屑病患者报告瘙痒,而50%的人报告皮肤疼痛。瘙痒的平均NRS为4.52±2.88分,4IIS的平均得分为6.79±4.37分。就皮肤疼痛的强度而言,平均NRS为2.42±2.96分;SF-MPQ评分平均为4.84±7.51分;VAS评分为1.92±2.65分.此外,17%的成人银屑病患者报告神经性疼痛。在84.9%的参与者中,皮肤疼痛与受瘙痒影响的区域同时发生,而18.9%的患者表现出涵盖所有瘙痒区域的皮肤疼痛。疼痛NRS与SF-MPQ显著相关(r=0.531,p<0.001),VAS(r=0.779,p<0.001),痒NRS(r=0.551,p<0.001),和4IIS(r=0.569,p<0.001)。疼痛NRS与PASI或疾病持续时间之间未发现关联。结论:轻度皮肤疼痛和中度瘙痒是银屑病患者的常见症状。皮肤疼痛和瘙痒之间的强相关性可以通过神经源性炎症的过程来解释。
    Background: Psoriasis is a common inflammatory disease that is often associated with itch and pain. This study aimed to evaluate the clinical characteristics of skin pain among patients with psoriasis. Materials: A total of 106 patients diagnosed with psoriasis were included in the study (34% female; mean age 42.1 ± 13.0 years). Disease severity was assessed using the Psoriasis Area and Severity Index (PASI). Itch severity was evaluated using the numeric rating scale (NRS) and 4-Item Itch Score (4IIS). The intensity of skin pain was measured through the NRS, short-form McGill pain questionnaire (SF-MPQ), visual analog scale (VAS), and Douleur Neuropathique-4 questionnaire (DN4). Results: In the past week, 84.9% of psoriasis patients reported itch, while 50% of them reported skin pain. The average NRS for itch was 4.52 ± 2.88 points, and the 4IIS yielded a mean score of 6.79 ± 4.37 points. In terms of the intensity of cutaneous pain, the mean NRS was 2.42 ± 2.96 points; the SF-MPQ score averaged 4.84 ± 7.51 points; and the VAS score was 1.92 ± 2.65 points. Furthermore, 17% of adult psoriasis patients reported neuropathic pain. In 84.9% of the participants, skin pain was concurrent with areas affected by itch, while 18.9% of patients exhibited cutaneous pain encompassing all itchy areas. The pain NRS demonstrated significant correlations with the SF-MPQ (r = 0.531, p < 0.001), VAS (r = 0.779, p < 0.001), itch NRS (r = 0.551, p < 0.001), and 4IIS (r = 0.569, p < 0.001). No association was found between the pain NRS and PASI or disease duration. Conclusions: Skin pain of mild intensity and itch of moderate intensity are prevalent symptoms in psoriasis patients. Strong correlations between skin pain and itch can be explained by the process of neurogenic inflammation.
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  • 文章类型: Journal Article
    扁桃体切除术已被认为是解决银屑病的潜在干预措施;然而,其对银屑病发展的预防作用尚不清楚。这项研究旨在调查在接受扁桃体切除术的韩国成年人群中发生迟发性牛皮癣的风险。利用了2002年至2019年韩国国家健康保险服务-健康筛查队列的数据。在总共514866名参与者中,使用基于倾向评分的重叠加权调整,将1082名年龄在40岁或以上的扁桃体切除术参与者与4328名对照参与者进行匹配。计算扁桃体切除术组和对照组的银屑病发生率和风险比(HR)。扁桃体切除组银屑病发生率为1.30%,对照组为1.20%。接受扁桃体切除术的患者与对照组的银屑病发生率(重叠加权HR=1.08,区间的95%置信区间=0.69-1.69,p=0.732)没有显着差异。发生银屑病的累积概率在两组之间没有差异(Log-rank检验:p=0.440)。这些发现在按年龄划分的亚组中是一致的,性别,收入,和居住地区。我们发现扁桃体切除术对韩国成年人群的晚发性牛皮癣的发展没有预防作用。
    Tonsillectomy has been suggested as a potential intervention to resolve psoriasis; however, its preventive effects on the development of psoriasis remain unclear. This study aimed to investigate the risk of developing late-onset psoriasis among a Korean adult population who had undergone tonsillectomy. Data from the Korean National Health Insurance Service-Health Screening Cohort between 2002 and 2019 were utilized. Out of a total of 514,866 participants, 1082 participants aged 40 years or older who had undergone tonsillectomy were matched with 4328 control participants using overlap weighting adjustment based on the propensity score. The incidence and hazard ratio (HR) of psoriasis were calculated for both tonsillectomy and control groups. The incidence rates of psoriasis were 1.30% in the tonsillectomy group and 1.20% in the control group. The incidence of psoriasis (overlap-weighted HR = 1.08, 95% confidence of interval = 0.69-1.69, and p = 0.732) did not differ significantly between the patients who underwent tonsillectomy and those in the control group. The cumulative probability of developing psoriasis was not different between the two groups (Log-rank test: p = 0.440). These findings were consistent across subgroups divided by age, sex, income, and region of residence. We found that tonsillectomy did not confer a preventive effect on the development of late-onset psoriasis in the Korean adult population.
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  • 文章类型: Journal Article
    在过去的十年里,我们对银屑病发病机制的认识已经取得了重大进步,导致多种改变游戏规则的疗法的发展。虽然牛皮癣主要影响皮肤,它越来越被认为是一种可以影响皮肤以外的全身性疾病。肥胖与更严重的牛皮癣有关,并可能使牛皮癣患者的全身性炎症和代谢功能障碍恶化。这两个条件之间联系的确切机制还没有完全理解,但人们认为慢性炎症和免疫失调起作用。在这次审查中,我们研究了现有的关于银屑病和肥胖致病过程交叉的知识体系.还将讨论生物疗法减少银屑病患者全身性和肥胖相关炎症的能力。
    In the past decade, our understanding of psoriasis pathogenesis has made significant steps forward, leading to the development of multiple game-changing therapies. While psoriasis primarily affects the skin, it is increasingly recognized as a systemic disease that can have effects beyond the skin. Obesity is associated with more severe forms of psoriasis and can potentially worsen the systemic inflammation and metabolic dysfunction seen in psoriatic patients. The exact mechanisms underlying the link between these two conditions are not fully understood, but it is believed that chronic inflammation and immune dysregulation play a role. In this review, we examine the existing body of knowledge regarding the intersection of pathogenic processes responsible for psoriasis and obesity. The ability of biological therapies to reduce systemic and obesity-related inflammation in patients with psoriasis will be also discussed.
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